The ergot alkaloids have been known for centuries and are recognized as possessing a wide variety of physiological properties. Several of the naturally occuring ergot alkaloids have been used as oxytocic agents. Recently, it has been found by Clemens, Semonsky, Meites, and their various co-workers that many ergot-related drugs, including those having either the ergoline or the 2,3-dihydro-9-ergolene ring system, are prolactin inhibitors. Certain 2,3-dihydroergolenes, available from total synthesis, have displayed decreased potency as prolactin inhibitors. It is therefore often desirous to convert such 2,3-dihydroergolenes to the corresponding unsaturated derivatives.
2,3-Dihydro-6-methyl-8-hydroxy-9-ergolene was first prepared by Kornfeld et al., as described in J. Am. Chem. Soc. 78, 3087 (1956). Oxidation of this ergolene not only removed the hydrogen atoms at the 2 -and the 3-position, but additionally converted the 8-hydroxyl group to a ketone. Reduction of the ketone generally provided a mixture of epimeric 6-methyl-8-hydroxy-9-ergolenes which had to be separated into the corresponding 8.beta.-hydroxy and the 8.alpha.-hydroxy-9-ergolenes.
An object of this invention is to provide a process for converting 2,3-dihydro-6-methyl-8-hydroxy-9-ergolene to the corresponding 2,3-dehydro derivative without forming an intermediate 8-ketone. This and other objects will become apparent from the detailed description presented hereinbelow.